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Santorsola, M.

Publications and source records attributed to Santorsola, M..

4 recordsLinked to original sources

Eduomics: a Nextflow pipeline to simulate -omics data for education

Moving past learning just algorithms and code is a key challenge of bioinformatics education: the ideal goal is for students to acquire higher-order knowledge such as the ability to solve biological problems with the appropriate tools, and more importantly learn to interpret the results in the broader context where bioinformatics is needed. To design such a teaching and learning experience, data simulations play a key role: however, there is a massive barrier to adoption. Different data types are produced by different tools, requiring educators to learn each of them and adapt their workflow to the necessary dependencies, requirements and input files. Additionally, most existing data simulation solutions are meant for benchmarking and methods development rather than education and cannot provide the context needed to teach students the critical interpretation skills they need to move beyond problem-based learning to what we call storyline-based learning. A significant effort must be placed also when many datasets with the same characteristics are needed, such as in tutoring or assessment in higher education. Here, we present eduomics: a Nextflow pipeline meant to automate the simulation workflow for both genomic and transcriptomic next-generation sequencing data, and to produce realistic clinical scenarios to provide students with clues and a biomedical story necessary for the interpretation of their results. Eduomics removes barriers to adoption, by requiring the user to just decide which chromosome datasets should be simulated on, and which type of data they would like to simulate. There is no need to learn specific tools and resolve their dependencies. The use of Gemini API provides an innovative approach to generate plausible clinical scenarios, consistent with the genes where either a pathological mutation or differential expression has been simulated. With eduomics, we offer an accessible and scalable solution to design comprehensive learning experiences and innovate bioinformatics education. Author SummaryModern bioinformatics education faces a dual challenge: students must learn how to analyse data and interpret results within the biological problems they aim to solve, while instructors who wish to design such a comprehensive learning experience should introduce appropriately simulated data in their teaching. However, the complexity of existing simulation tools is an often daunting barrier to overcome: current solutions require different software for different data types and provide no support for teaching interpretation skills. Most available simulators were designed for benchmarking and method development, not for education: therefore they lack the biological and clinical context needed to move beyond the traditional problem-based learning. To address these challenges, we developed eduomics, a Nextflow-based end-to-end pipeline that automates the simulation of genomic and transcriptomic data in a fully automated manner for educational use. Educators only need to choose the type of data to simulate, while the pipeline handles all underlying tools and dependencies. As a groundbreaking element, we integrated the Google Gemini API to generate patient-inspired clinical scenarios that gives students realistic clues and a biomedical narrative in which to interpret the results. This approach complements the traditional problem-based learning by offering a more complete, storyline-based learning experience. By combining automated data simulation and clinical storytelling, eduomics provides an accessible and scalable solution that support an engaging and immersive learning experience for both educators and students.

bioinformatics↗

Adaptive disorder as the hallmark of nanobodies antigen-binding loops

Nanobodies are antigen-binding proteins of great interest as diagnostics and therapeutics. Accurate and fast characterization of their complementarity-determining regions (CDRs) is crucial to uncover the principles guiding their design. Yet, this task remains challenging, as random recombination and somatic mutations generate highly diverse CDR sequences that escape motif-based or structure-prediction approaches currently used to identify them. To overcome this hurdle, we employed two independent strategies that converged on the same conclusion. At the sequence level, we developed a deep learning model to identify nanobody CDRs directly from the primary sequence. At the structural level, we applied an energy decomposition method, revealing CDRs as residues highly uncoupled to the rest of the fold. Explainability analyses showed the network captured intrinsic CDR properties, which notably aligned with these energy values. CDRs emerge as fuzzy regions capable of adopting diverse conformational ensembles, from which a preferred state is selected upon antigen binding. This finding supports a model where chaos in both sequence and structure appears adaptive and disorder emerges as the hallmark of nanobody CDRs. This work aims to advance the definition of rules for the design of antigen binding regions, paving the way for the next-generation immune diagnostics and therapeutics.

immunology↗

Spiroplasma impairs testes gene expression in Glossina fuscipes fuscipes

Glossina fuscipes fuscipes is a riverine tsetse fly species, the primary vector of human and animal trypanosomiasis in Sub-Saharan Africa. Controlling tsetse fly populations is crucial for mitigating the socio-economic impact of this disease, as effective treatments remain challenging. Indeed, the development of control strategies is hindered by the species unique reproductive biology: adenotrophic viviparity, in which the female retains and nourishes the developing larva in her uterus throughout the pregnancy. The discovery of Spiroplasma in some G. f. fuscipes populations has drawn attention as a potential tool to enhance tsetse fly control strategies. Although Spiroplasma does not exhibit in G. f. fuscipes the male-killing phenotype observed in Drosophila melanogaster, evidence suggests that it may confer refractoriness to Trypanosoma infection. This has led to further investigations into its broader effects on G. f. fuscipes biology, particularly its potential impact on Glossina reproductive fitness. In this study, we considered Spiroplasma effect on the male reproduction. For this, we performed a differential gene expression analysis on testes and male accessory glands (MAGs) between Spiroplasma-infected and uninfected males. A significant downregulation of genes was observed in testes while a minor effect has been detected on MAGs. Downregulation of testes genes associated with functions related to sperm motility, energy metabolism, and mitochondrial function has been observed. Additionally, differentially expressed genes involved in antimicrobial activity and circadian rhythm regulation were observed. These findings provide valuable insights into the potential fitness costs of Spiroplasma infection for the fly and its implications for the bacterium use as biological control strategies targeting G. f. fuscipes.

genomics↗

hgtseq: a standard pipeline to study horizontal gene transfer

Horizontal gene transfer (HGT) is well described in prokaryotes, it plays a crucial role in evolution, and has functional consequences in insects and plants: less is known about HGT in Humans. Studies have reported bacterial integrations in cancer patients, and microbial sequences have been detected in data from well-known Human sequencing projects. Few of the existing tools to investigate HGT are highly automated. Thanks to the adoption of Nextflow for life sciences work-flows, and the standards and best practices curated by communities such as nf-core, fully automated, portable, and scalable pipelines can now be developed. Here we present nf-core/hgtseq, to facilitate the analysis of HGT from sequencing data in different organisms. We showcase its performance by analysing six exome datasets from five mammals. Hgtseq can be run seamlessly in any computing environment and accepts data generated by existing exome and whole-genome sequencing projects: this will enable researchers to expand their analyses into this area. Fundamental questions are still open, about the mechanisms and the extent or the role of horizontal gene transfer: by releasing hgtseq we provide a standardised tool which will enable a systematic investigation of this phenomenon, thus paving the way for a better understanding of HGT.

bioinformatics↗